The Hofstadter energy spectrum provides a uniquely tunable system to study emergent topological order in the regime of strong interactions. Previous experiments, however, have been limited to the trivial case of low Bloch band filling where only the Landau level index plays a significant role. Here we report measurement of high mobility graphene superlattices where the complete unit cell of the Hofstadter spectrum is accessible. We observe coexistence of conventional fractional quantum Hall effect (QHE) states together with the integer QHE states associated with the fractal Hofstadter spectrum. At large magnetic field, a new series of states appear at fractional Bloch filling index. These fractional Bloch band QHE states are not anticipated by existing theoretical pictures and point towards a new type of many-body state.
Abstract Photothermal therapy (PTT) using nanoparticles has been extensively studied to eliminate cancer cells. PTT is a local therapy with less harmful systemic effect compared to other treatments such as chemotherapy. Iron oxide nanoparticles have been used as a photothermal agent to absorb and convert near infrared (NIR) light to thermal energy resulting in temperature increase. However, to produce high temperature, high-energy laser power is necessary which causes non-specifically damage to normal tissues surrounding tumor tissue. We report herein the new type of nanostructure called “Janus”, which composed of iron oxide and gold nanoparticles in asymmetrical fashion to significantly enhance the PTT effect compared to traditional iron oxide nanoparticles. The higher PTT efficiency of Janus nanostructure is resulted from the coupling effect between iron oxide and gold nanoparticles. In addition, Janus nanostructures also provide a great magnetic resonance imaging (MRI) capability and a photothermal effect, which could be used in cancer theranostics. The Janus structure (JNS) was generated using 15 nm iron oxide (IONP) and 5 nm gold nanoparticles (AuNP) that were encapsulated in a thermo-cleavable polymer by using seed-mediated self-assembly method. JNS was determined by transmission electron microscope (TEM) and x-rays diffraction elemental mapping (XED). It clearly shows that IONPs and AuNPs rearrange in an asymmetrical structures. TheT2 relaxivity of JNS at different iron concentrations was determined. JNS yield almost 3 times higher R2 relaxation compared to Feridex, which is a commercially available iron oxide nanoparticles for MRI contrast agent. PTT efficiency of JNS was investigated in SUM 159 breast cancer cell line by irradiating the cell with 885 nm laser at 0.45 watt for 10 minutes. Interestingly, JNS generate a significantly higher temperature after 10 minutes of laser irradiation compared to IONPs alone, AuNP alone, and the mixture solution of IONP and AuNP at the same concentration of either iron or gold. We also examined the cell viability by alamar blue assay after photothermal treatment. SUM 159 cells were treated with JNS, IONP micelles alone, AuNP micelles alone, a mixture solution of IONP micelles and AuNP micelles. The cells treated with JNS have significant lower viability among other groups due to higher PTT efficiency.. We anticipate that AuNPs and IONPs could have an electron coupling effect among particles resulting in the enhanced temperature for PTT for cancer treatment. In conclusion, JNS provide a great MR imaging capability and PTT efficiency, which could be potentially applied for cancer treatment. Citation Format: Kanokwan Sansanaphongpricha, Hongwei Chen, Kai Sun, Bo Wen, Duxin Sun. Janus nanostructures for magnetic resonance imaging and enhanced photothermal therapy for cancer theranostics. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1331.
Abstract The very poor hot workability of hard-to-deform GH4742 alloy is represented in the aspects of very narrow available deformation temperature range, high deformation-resistant force and low thermoplasticity. In this paper, the hot deformation behavior of a Ni-based superalloy was studied in the temperature range of 1060-1160°C and strain rate range of 0.05-0.5 s −1 using hot compression tests. A hot deformation equation is given to characterize the dependence of peak stress on the temperature and strain rate. Results of hot compression test of the GH4742 alloy were indicated that the hot deformation is sensitive to temperature and strain rate. A special heat treatment to change the ingot microstructure is proposed to improve the hot workability of the GH4742 alloy. Modified microstructure induces that the hot deformation flow stress of GH4742 alloy was decreased effectively and hot deformation plasticity was increased obviously.
As an orally administered, locally acting gastrointestinal drug, mesalamine products are designed to achieve high local drug concentration in the gastrointestinal (GI) tract for the treatment of ulcerative colitis. The aim of this study was to directly measure and compare drug dissolution of three mesalamine formulations in human GI tract and to correlate their GI concentration with drug concentration in plasma. Healthy human subjects were orally administered Pentasa, Apriso, or Lialda. GI fluids were aspirated from stomach, duodenum, proximal jejunum, mid jejunum, and distal jejunum regions. Mesalamine (5-ASA) and its primary metabolite acetyl-5-mesalamine (Ac-5-ASA) were measured using LC–MS/MS. GI tract pH was measured from each GI fluid sample, which averaged 1.82, 4.97, 5.67, 6.17, and 6.62 in the stomach, duodenum, proximal jejunum, middle jejunum, and distal jejunum, respectively. For Pentasa, high levels of 5-ASA in solution were observed in the stomach, duodenum, proximal jejunum, mid jejunum, and distal jejunum from 1 to 7 h. Apriso had minimal 5-ASA levels in stomach, low to medium levels of 5-ASA in duodenum and proximal jejunum from 4 to 7 h, and high levels of 5-ASA in distal jejunum from 3 to 7 h. In contrast, Lialda had minimal 5-ASA levels from stomach and early small intestine. A composite appearance rate (CAR) was calculated from the deconvolution of individual plasma concentration to reflect drug release, dissolution, transit, and absorption in the GI tract. Individuals dosed with Pentasa had high levels of CAR from 1 to 10 h; individuals dosed with Apriso had low levels of CAR from 1 to 4 h and high levels of CAR from 5 to 10 h; Lialda showed minimal levels of CAR from 0 to 5 h, then increased to medium levels from 5 to 12 h, and then decreased to further lower levels after 12 h. In the colon region, Pentasa and Apriso showed similar levels of accumulated 5-ASA excreted in the feces, while Lialda showed slightly higher 5-ASA accumulation in feces. However, all three formulations showed similar levels of metabolite Ac-5-ASA in the feces. These results provide direct measurement of drug dissolution in the GI tract, which can serve as a basis for investigation of bioequivalence for locally acting drug products.
Expression levels of the cell adhesion molecule syndecan-1 (SDC1) have been shown to be inversely proportional to tumor differentiation and prognosis. However, its role in the development of gallbladder cancer (GBC) remains unclear.We knocked down SDC1 in GBC cells by RNA interference and determined its roles in cell proliferation, apoptosis, invasion, and migration by Cell Counting Kit-8, colony-formation, flow cytometry, Hoechst 33342 staining, transwell invasion, and scratch wound assays. Expression levels of epithelial-mesenchymal transition (EMT)-related and extracellular signal-regulated kinase (ERK)/Snail pathway proteins were determined by western blotting and immunofluorescence.Cell proliferation, invasion, and migration were all increased in GBC cells with SDC1 knockdown, compared with cells in the blank control and negative control groups, but apoptosis was similar in all three groups. E-cadherin and β-catenin expression levels were significantly lower and N-cadherin, vimentin, p-ERK1/2, and Snail expression were significantly higher in the SDC1 knockdown group compared with both controls, while ERK1/2 levels were similar in all groups. Reduced E-cadherin and increased vimentin levels were confirmed by immunofluorescence.SDC1 knockdown promotes the proliferation, invasion, and migration of GBC cells, possibly by regulating ERK/Snail signaling and inducing EMT and cancer cell invasion.
A novel complex, [CuI2L2]2[Mo8O26] (1), was hydrothermally synthesized by using ammonium molybdate, copper nitrate and 1,3-bis(imidazol-l-yl-methyl)benzene. Complex 1 exhibits a new 3D (3,4,6)-connected topological structure with a Schlafli symbol of (4·6·8)2(42·64·83·102·123)(44·62)2, which is constructed by [Mo8O26]4− anions linking a [4 + 4] metallomacrocycle.
Abstract STAT3 (signal transducer and activator of transcription 3) is a transcription factor and a promising therapeutic targets for cancer and other human diseases. We have previously reported the discovery of SD-36 and SD-91 as potent, selective and highly efficacious STAT3 degraders. In the present study, we report the discovery of highly potent, selective and efficacious new STAT3 degraders. These STAT3 degraders were designed using our high-affinity STAT3 ligands and high-affinity VHL-1 ligands, with UM-STAT3-3100 being the best. In direct comparison, UM-STAT3-3100 is >10-times more potent than SD-36 and SD-91 in inducing STAT3 degradation in cells and are highly selective over other STAT members in vitro and in vivo. A single intravenous administration of UM-STAT3-3100 resulted in complete and long-lasting depletion of STAT3 protein for >48 hrs in tumor and native tissues. Weekly administration of UM-STAT3-3100 at 10 mg/kg achieved complete and long-lasting tumor regression in animal models of human cancer without any signs of toxicity. UM-STAT3-3100 is a promising compound for extensive evaluation for the treatment of human cancers and other human diseases in which STAT3 plays a key role. Citation Format: Ranjan K. Acharyya, Longchuan Bai, Haibin Zhao, Dimin Wu, Metwally Hoda, McEachern Donna, Wen Bo, Duxin Sun, Shaomeng Wang. Discovery of potent and highly efficacious STAT3 PROTAC degraders capable of achieving long-lasting tumor regression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4509.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)